You are here:
Endocrine Activity of Bisphenol S (BPS) Using In Vitro Estrogenic/Anti-Androgenic Transcriptional Activation Assays and the In Vivo Uterotrophic Assay
Citation:
Conley, J., M. Cardon, N. Evans, E. Gray, P. Foster, J. Furr, B. Hannas, V. Sutherland, AND V. Wilson. Endocrine Activity of Bisphenol S (BPS) Using In Vitro Estrogenic/Anti-Androgenic Transcriptional Activation Assays and the In Vivo Uterotrophic Assay. Society of Toxicology (SOT) Annual Meeting, SAN DIEGO, CA, March 22 - 26, 2015.
Impact/Purpose:
The current study will provide novel information on the in vitro and in vivo reproductive toxicity of individual plasticizer alternatives and mixtures of pasticizers currently being used to replace BPA in consumer products. BPS exposures are on the increase due to its use as a replacement, but there are no data on it's potential toxicity after oral exposure. The EPA nominated BPS for study at the NTP and they are planning to conduct a series of toxicity and cancer studies with BPS. The data from this project will enable the NTP to determine if this chemical has potential toxicity as an estrogen following exposure via a relevant route of administration and facilitate their dose setting in the toxicity studies.
Description:
Bisphenol A (BPA) is gradually being phased out of many consumer products and processes leading to potential increases in human and environmental exposures to relatively understudied replacement compounds, including Bisphenol S (BPS). Research from our lab has shown that BPA and Bisphenol AF (BPAF) display relatively similar estrogenicity and anti-androgenicity in vitro (BPAF ~10-fold more potent), whereas BPAF stimulated uterine weight gain with oral administration in vivo (≥50 mg kg-1 d-1) but BPA had virtually no effect. Here we asked, does BPS behave similarly to either BPA or BPAF in vitro and/or in vivo estrogenicity/anti-androgenicity assays? We conducted estrogen receptor (ER) transactivation assays utilizing T47D-kbluc cells and androgen receptor (AR) antagonism assays utilizing transient transduction of CV-1 cells with chimp AR. We found that BPS induced estrogen-dependent gene expression in vitro at concentrations similar to BPA and BPAF (≥300 nM), whereas BPS was 100-fold less potent than BPAF in the AR antagonist assay and only displayed anti-androgenicity at the highest concentration tested (100 µM). Cytotoxicity was not responsible for the anti-androgenic effects. Since BPA and BPS are currently in use, exposures to mixtures of BPA, BPS, other replacement compounds, and associated metabolites are possible. In order to determine if a mixture of BPA and BPS acts in an additive, antagonistic or synergistic manner, we conducted ER transactivation assays with binary mixtures of BPA and BPS (8x8 factorial design) and found that these compounds conformed to dose addition model predictions for ER agonism in vitro. In addition, we are examining the effects of BPS and mixtures of BPS with other chemicals in vivo using oral exposures to determine the estrogenicity of this chemical when administered via a relevant route of exposure. Abstract does not reflect U.S. EPA policy.